Biological contributions of articular chondrocytes to degenerative joint disease will continue to be studied in organ and cell culture of cartilage. Phenotypic expression of collagen and glycosaminoglycan species occurs in non-dividing cultures but not under monolayer conditions. Six specific goals are projected the next phase of the project: 1. Studies of DNA repair in the aging of articular chondrocytes will be extended to organ and suspension cultures. The latter are designed to bypass the "dedifferentiation" and anchorage-related changes that occur in monolayer culture. 2. The effects of four macromolecular serum factors (insulin, PDGF, somatomedin, DGF) on growth and differentiation of articular chondrocytes will be studies in organ and suspension cultures. The purpose is to explicate the contributions of cartilage matrix and of "dedifferentiation" on the response of this cell type to the factors. 3. The commitment-progression sequences of platelet derived frowth factor and somatomedin in the initiation of DNA synthesis by articular chondrocytes will be evaluated in monolayer culture. 4. Xenografts of articular chondrocytes into athymic nude mice will be employed to examine three phenomena: (a) the reversibility of dedifferentiation of articular chondrocytes; (b) aging of articular chondrocytes; (c) possible application to mechanisms of calcification of cartilage 5. The effect of hemoglobin-derived Fe on the degeneration of articular chondrocytes will be studied in organ culture and in vivo in rabbits. The purpose is to determine whether there is a rationale for the use of iron chelators in the management of hemophilic arthropathy. 6. The collagens in human osteoarthritic specimens will be examined immunohistochemically to test the concept that dedifferentiation of articular chondrocytes occurs in vivo.